Objective: To evaluate the efficacy and safety of etoposide/methotrexate/actinomycin D (MEA regimen) as initial chemotherapy and 5-fluorouracil/actinomycin D (FA regimen) as salvage chemotherapy for high-risk gestational trophoblastic tumor (GTT).
Study design: From 1985 to 2001, 36 patients with World Health Organization (WHO)--defined high-risk GTT were treated with MEA or FA at Chiba University Hospital. Thirty-three patients were initially treated with MEA. FA was administered to 11 patients; 1 had had no previous chemotherapy, 7 had developed drug resistance to MEA, 1 had relapsed following MEA, and 2 had relapsed following etoposide/methotrexate/actinomycin D/ cyclophosphamide/vincristine (EMA/CO) combination chemotherapy.
Results: The primary remission rate with MEA was 69.7% (23 of 33). With FA the survival rate was 81.8% (9 of 11) for a mean follow-up period of 11.5 years. Two patients died due to multidrug resistance, and 2 patients relapsed subsequently. The 2 relapse cases were successfully salvaged again with MEA. The toxicity of FA was evaluated in 89 cycles. Myelosuppression seemed to be the dose-limiting toxicity, and the incidence of WHO grade 4 leukocytopenia and thrombocytopenia were 5.6% and 3.4%, respectively.
Conclusion: Although etoposide-containing chemotherapy is currently the most effective and well tolerated regimen for high-risk GTT, 20-30% of patients develop drug resistance to these regimens. Salvage combination chemotherapy with FA is effective for refractory patients, and the toxicity is predictable and manageable.